Many modern medical procedures require the use of tubing sets of varying complexity to withdraw fluid from a patient, or to administer fluid to a patient, or to do both. Such procedures include intravenous feeding, blood transfusions and blood processing, and both peritoneal dialysis and hemodialysis. Typically, a catheter is temporarily or semi-permanently implanted in the patient such as by cannulating a vein in the case of hemodialysis or a catheter is implanted in a peritoneal cavity in the case of peritoneal dialysis. The catheter extends from the implant site to outside the body, where it is connected in some manner to the appropriate tubing set necessary for the procedure that is to be performed.
The configuration and complexity of tubing sets are vastly different depending upon the particular medical procedure for which they are designed and also depending in the manufacturer of the other extracorporeal elements used in the procedure. For example, a hemodialysis tubing set is much different from a peritoneal dialysis tubing set because of the different nature and requirements of hemodialysis as compared to peritoneal dialysis, and a peritoneal dialysis tubing set made by one manufacturer for use with its peritoneal dialysis cycler machine may be much different from a peritoneal dialysis tubing set made by another manufacturer for use with the other manufacturer's peritoneal dialysis cycler machine.
In hemodialysis, the patient's blood is cleansed by drawing it out of the patient though a catheter and passing it through an artificial kidney. The artificial kidney includes a semi-permeable membrane which removes impurities and toxins by a process of diffusion. The purified blood is then returned to the patient. A hemodialysis tubing set is used to transport the blood between the catheters and the artificial kidney. Patients in hemodialysis treatment typically require treatment several times a week for several hours each time.
In peritoneal dialysis, a peritoneal dialysis solution is infused into the patient's peritoneal cavity and allowed to reside there for a "dwell time" during which blood impurities diffuse through the peritoneal membrane into the dialysis solution. The dialysis solution with the collected impurities is then removed from the peritoneal cavity and discarded. In Continuous Ambulatory Peritoneal Dialysis ("CAPD") the infusion of dialysis solution into and out of the peritoneal cavity is accomplished throughout the day while the patient goes about a fairly normal routine. In Intermittent Peritoneal Dialysis ("IPD") large amounts of dialysis solution (up to 40 liters) are cycled through the patient's peritoneal cavity over a 4 to 24 hour period. In Continuous Cycling Peritoneal Dialysis ("CCPD") the dialysis treatment is more or less continuous, with dwell times of 3 to 4 hours at night. Then, throughout the waking time of the patient, a single dose of dialysis solution is retained within the patient.
In both IPD and CCPD an automated dialysis apparatus operates in generally the same manner. The dialysis solution and "tubing administration set" or simply "tubing set" is integrated with the valving, heating and control functions associated with the automated apparatus. In many of the systems, premeasured amounts of dialysis solution are either pumped or delivered by gravity flow to a heating station. At the heating station the solution is warmed to body temperature in order to prevent the uncomfortable sensation of introducing room temperature or cooler solution into the peritoneal cavity. The warmed solution is then allowed to enter the patient via a catheter implanted in the patient's peritoneal cavity. After a period of time (the "dwell period"), the solution is drained from the patient into a spent solution container.
In IPD, a large amount of solution is cycled in this manner over a relatively short period of time. Once treatment is completed, the patient is unencumbered for at least a few days. A disadvantage is the large amount of dialysis solution that must be utilized. Bags cumulating to at least 40 liters of solution can be difficult to lift for a patient in a weakened condition.
In CCPD and CAPD methods, the same efficiency of results is obtained by increasing the dwell time of the dialysis solution within the peritoneal cavity. The total amount of solution required can therefore be significantly reduced. The obvious disadvantage, is that there is no "down time" for the treatment.
One of the significant items of expense in peritoneal dialysis of all types is the tubing set. Tubing sets vary widely depending on the type of peritoneal dialysis with which they are used and the brand of cycling equipment with which they are used, but all of them have a cost that is significant, especially when one considers that they are used between several times a week and several times a day for years. Tubing sets must be sterile, and so they are normally used once and then discarded. Thus, for example, a tubing set that costs only ten dollars becomes a fairly major expenditure for a patient that receives dialysis once a day, if that dialysis continues for years as it very often does.
Many of the tubing sets used with these dialysis procedures or with other medical procedures involving extracorporeal treatment of fluid, use releasable connectors. For example, a hemodialysis patient or a peritoneal dialysis patient will often have a semi-permanent implanted catheter in the vascular system or peritoneal cavity, respectively, which extends to outside the patient. The exterior end of the catheter is capped with a removable cap, or is attached to a tubing segment which in turn is capped with a removable cap. It is very important that these ends and caps be antiseptic to prevent the transmission of disease, especially since many of these patients are already in frail health. The connections must also be mechanically strong and secure to prevent accidental disconnection during the procedure.
For CAPD connectors in particular, the connectors need to be secure and to provide an anti-bacterial effect in the connector. During CAPD, a certain quantity of sterile dialysis fluid is brought from a plastic bag through a tubing system into the peritoneal cavity. After a period of some time, the fluid is transferred from the cavity back to a receiving bag, possibly the same bag. In the meantime, an osmotic equilibrium is accomplished between the waste substances accumulated in the blood of the uraemic patient and the dialysis fluid. By replacing the dialysis fluid with fresh dialysis fluid after several hours, one repeatedly removes a portion of the accumulated waste substances from the blood. Because the dialysis fluid is changed four or five times a day, thousands of connections and disconnections of dialysis bags may be necessary per year. It is absolutely necessary to carry out a sterile connecting and disconnecting procedure. Since the dialysis fluid does not include white blood cells, it is clear that any infectious agents such as bacteria introduced during the connecting procedure, even if there are very few, may multiply unhindered inside the peritoneal cavity of the patient. The problem is compounded by the fact that CAPD treatment often takes place in the patient's non-sterile home and is performed by the patient himself. It is believed that about 60% of CAPD patients suffer from peritonitis within two years after starting treatment.
Other medical treatments may lead to infection less often than CAPD; however, it is still desirable that contamination be held at a minimum. If infectious agents are introduced into the bloodstream during the administration of intravenous fluids or medication, for example, they normally come in contact with white blood cells which strongly counteracts the infection. However, there is a considerable number of patients suffering from a serious reduction in the number or the immunological activity of white blood cells, such as some cancer patients and acquired immune deficiency patients. The introduction of a single bacterium into the body of this group of patients can cause dangerous infections. Various types of connector assemblies attempt to address these problems, but none is perfect.
In a barrier connector assembly of the prior art, both sides of the connector are provided with a deformable barrier. Before connecting the two sides, the barriers are first brought into contact with each other, after which the fixation points of these barriers will not change their mutual position. One of the connectors comprises a telescopically movable penetration tube which is pushed through both barriers and the front end is slid into the other connector. An example of this type of connector assembly is disclosed in U.S. Pat. No. 4,334,551. In coupling the connectors, a sterile connection might be achieved if both barriers have been sprayed beforehand with a sterilizing liquid. However, there is the risk that the penetration tube after penetrating the first barrier, pushes away the second barrier. Then, unsterile air can pass into the resulting space between the barriers. Also, during the disconnection procedures the barriers may be pulled loose from each other by the retracting penetration tube so that unsterile air is sucked between the barriers to contaminate the outside of the penetration tube.
Other commercial attempts at minimizing environmental and touch contamination of a connector apparatus requires the patient to remove povidone iodine antiseptic sponges from a container, to separately remove sterile gauze sponges from another container or envelope, to apply the swab dressing to the spike connector site and to place the gauze sponge around the dressing and then to peel the backing off, and to tape and separately apply it around the dressing and gauze sponges to hold them in place around the connection. Thus, not only must the patient make the tubing connection, inserting the male or spike portion of the connection, but the patient must then immediately manually carry out the several described steps to establish and maintain an antiseptic connection of the connector while the connector remains exposed to the atmosphere. Although the components of the connector are provided in a kit, the components nevertheless require considerable handling.
The difficulties in attempting to utilize antiseptic sponges are addressed in U.S. Pat. No. 4,402,691 through the use of a firm plastic protection enclosure barrier device for surrounding the connection site and providing the site with an antiseptic barrier. The barrier device--sometimes also identified as a clam shell approach--is comprised of a contoured plastic housing formed by mating cavity halves joined along a hinge line, and an absorbent member contained within the interior of the housing in a sealing tab attached to one of the housing halves for holding the two halves together when folded along the hinge line. In use, the absorbent member has antiseptic solution applied to the member and the housing is positioned to surround the connection site and is sealed in place to form a surrounding protective area barrier in seal.
Another prior art attempt in solving patient contamination in CAPD applications is provided in U.S. Pat. No. 4,432,764 which describes an antiseptic end cap for catheters in order to provide antiseptic catheter fittings.
Another antibacterial protective cap for connectors is provided in U.S. Pat. No. 4,440,207. A protective cap for the connector which securely receives and provides an antibacterial effect to the connector is provided wherein at least a portion of the protective cap interior is lined with an absorbent material which retains an antiseptic. The connector covered by the protective cap is thus placed in an anti-bacterial environment made possible by contact of the connector with the antiseptic-retaining absorbent material or from migration of the antiseptic or both.
Yet another attempt to avoid or to minimize the danger of peritoneal infections in CAPD procedures is presented by U.S. Pat. No. 4,810,241. An ambulatory dialysis system connector includes a cylinder containing a disinfecting solution which continuously bathes the male and female connectors of a tube during use. A highly absorbent material is packed in the cylinder and saturated with a disinfectant to bathe the male and female connectors. A connection is provided by a male fitting on the end of a tube connected to a container of dialysate fluid or in an abdominal opposing tube. The male connector is inserted into the female connector through the cylinder containing the absorbent material saturated with the disinfectant. The absorbent material is packed such that the male connector contacts the absorbent material during insertion to disinfect the opposing end simultaneously while connection is being made. Once the dialysate fluid is delivered to the patient through the connector, the tube may be pulled off the outer end of the male connector to remove the empty containers. The male connector is then sealed and capped.
In the field of implantable medical devices such as catheters, shunts and prostheses, there is a body of prior art on using bactericide metallic coatings to prevent infection. One metallic coating that has proven to be effective in such applications is silver. The term "oligodynamic" was coined in the eighteenth century to describe the remarkable antimicrobial properties of highly diluted silver in water. Later work confirmed these properties and led to the use of silver preparations as topical antimicrobial agents. In addition to its antimicrobial properties, silver is fairly biocompatible, is corrosion resistant and has good physical strength. Silver has been used in the form of organic salts, colloidal preparations, coatings and oxides, and by incorporating it into other materials such as being woven into polymers for use in sutures.
The mechanism of the antimicrobial activity of silver is not completely understood. The silver cation Ag.sup.+ is a reactive chemical species that binds strongly to electron donor groups containing sulfur, oxygen or nitrogen. Bacterial cell surfaces--and biological molecules in general--contain all these elements in the form of thiol, amino, imidazole, carboxylate and phosphate groups. In addition, silver can also act by displacing other essential metal ions such as Cu.sup.2+ or Zn.sup.+. Despite the fact that silver ions have antimicrobial effects that are at least as high as other heavy metals, it is clear that the toxic effects of silver ions on mammals is considerably lower. The main adverse effect of prolonged exposure to high levels of silver is argyria, which is a gray or black discoloration in subcutaneous tissue which may be localized in areas such as the hands or eyes or generalized over the whole body. Argyria is irreversible and perhaps unpleasant, but is thought to be purely a cosmetic phenomena with no associated functional disorders.
Silver coatings have been used for their antimicrobial properties in a number of in-dwelling or implanted catheters and catheter-related devices. For example, studies have demonstrated reduced catheter-associated bacteriuria in the use of silver alloy coated catheters. See "Silver Alloy Coated Catheters Reduce Catheter-Associated Bacteriuria", British Journal of Urology (1990) 65, 379-81. Antimicrobial silver-coated catheters are described in U.S. Pat. Nos. 4,5692,920 by Murtfeldt, 4,564,361 by Akiyama and 4,483,688 by Akiyama. In U.S. Pat. No. 4,886,505 by Haynes, there is described an antimicrobial catheter that relies upon a plurality of metals.
It is believed that the vast majority of prior art on antimicrobial silver coatings for medical devices is in the field of implants or in-dwelling devices such as urinary catheters or other catheters or cannulation devices such as those mentioned above, while there is very little prior art on silver coatings for extracorporeal devices. For example, the Haynes patent mentioned above states:
Preferred apparatuses in accordance with the invention are modified medical devices such as, for example, modified catheters, tracheal tubes, insulin pumps, would closures or drains, stopcocks, connectors, prosthetic devices, pacemaker leads, needles and the like. Most preferably, the apparatus of the invention remains in contact with the body for a period of time such that, without modification of the device surface in accordance with the invention, microorganism growth in association with the use of the device would occur. The most preferred apparatus of the invention is a modified catheter, in particular an indwelling urinary catheter.
The reason that antimicrobial silver coatings are largely limited to intracorporeal applications may be that until now the antimicrobial activity of the silver coatings were designed more to prevent on-going colonization than to act as a sterilant, and colonization occurs mainly in the colonization-conducive environment of inside the body rather than in a less-hospitable extracorporeal environment. Also, it has been thought that dissolution of the silver ions is important for effective antimicrobial activity, and dissolution occurs best in a liquid environment. See U.S. Pat. No. 4,886,505 by Haynes, mentioned above, and "Silver Accumulation in Pseudomonas Stutzeri AG259", Biology of Metals (1989) 2:168-173.
Other references in the field include U.S. Pat. Nos. 4,603,152 by Laurin, 5,049,139 by Gilchrist, 4,054,139 by Crossley and 4,559,033 by Stephen. The Laurin reference is fundamentally different from the present invention in that the surfaces coated with the antimicrobial agent are not guarded from touch contamination by any physical structure. Thus, the antimicrobial system depends entirely on the coating without any assistance from the configuration of the device. In the Gilchrist reference, the object is not to use an antimicrobial agent to prevent touch contamination of a connector surface, but to use the antimicrobial agent to sterilize contaminated fluid flowing through the connector. The Crossley and Stephen references are not concerned with antimicrobial agents applied to external connectors.
From the foregoing, it is clear that there is a need for an extracorporeal tubing connector that is simple and inexpensive to manufacture, easy to operate, and effective in preventing the transmission and not just colonization of microbes.